Validation of the Metastatic Formula:
A Method of Cervical Lymph Nodes
Assessment in Oral Cancer Patients
Ahmed E Ali1, Ahmed M Suleiman1, Mohammed M Elkulaibi2 and Yousif I Eltohami1*
1 Department of Oral and Maxillofacial Surgery, University of Khartoum, Sudan
2Department of Oral and Maxillofacial Surgery, Sana’a University, Yemen
Submission: November 01, 2018; Published: November 29, 2018
*Corresponding author: Yousif I Eltohami, Assistant professor of Oral and Maxillofacial Surgery, Faculty of dentistry, University of Khartoum, Sudan.
How to cite this article: A E Ali1, A M Suleiman, Md M Elkulaibi, Yousif I E. Validation of the Metastatic Formula: A Method of Cervical Lymph Nodes
Assessment in Oral Cancer Patients. Adv Dent & Oral Health. 2018; 10(1): 555777. DOI: 10.19080/ADOH.2018.10.555777
Background: The Metastasis Score (MS) had been introduced in 2007 as a new method for cervical nodes assessment in oral and maxillofacial cancer patients. The metastasis score (MS) was taken from the CT scan interpretation in the preoperative assessment and was found to be reliable.
Objective: To validate and evaluate the accuracy of the metastasis score (MS); a new method for cervical lymph nodes ASSESSMENT for metastasis in oral and maxillofacial cancer patients, in comparison to histopathology results.
Materials and Method: The study was conducted in Khartoum Teaching Dental Hospital, the main oral and maxillofacial referral center, during the period 2011-2013. Clinical investigation, CT scan, the metastasis scores (MS); from the CT scan interpretation, was calculated preoperatively on 25 patients who undergone neck dissection for primary head and neck malignancy.
Results:Seven cases had a score of (0-3) and 18 cases had a score of (6-10). Twelve (48.0%) cases were positive (+ve) for neck metastasis and 13 (53.0%) cases were negative (-ve) for neck metastasis in the histopathology results. The histopathology results for the cases with metastasis score (MS) (0-3) showed (-ve) results in all the cases with an accuracy of 100% as there was no (+ve) results. For metastasis score (MS) the group (6-10) the histopathology results were (-ve) in 6 cases with an accuracy of 33.3% and it was (+ve) in 12 cases with an accuracy of 66.7%. The Sensitivity (true +ve results) and specificity (true -ve results) of this study are 100% and 53% respectively.
Conclusion: The metastasis score (MS) predicts cervical metastasis with an accuracy of 100% for the group (0-3) and with an accuracy of 66.7% for the group (6-10) as there was an incidence of false positive results; nevertheless, this group mostly present with clinically positive neck where prophylactic neck dissection is indicated.
Cancer is a generic term for a large group of diseases that can affect any part of the body. Other terms used for cancer are malignant tumors and neoplasms. It is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in the year 2008. The mortality rate of it is increasing with an estimate of 13.1 million deaths by the year 2030 .
The characteristic features in the pathogenesis of cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries and which can then invade adjoining parts of the body and spread to other organs, such spread can be through lymphatic and blood vessels; this process is known as metastasis, which is the major cause of death from cancer .
Head and neck cancer (HNC) are the sixth most common cancer globally . HNC includes cancer originating in over 30
specific anatomical sites, most of them occur in the surface layers of the upper aerodigestive tract (UAT), the oral cavity, the upper part of the throat, the respiratory system (pharynx) and the voice box (larynx) .
The oropharynx is the third commonest site among males in the developing and industrialized countries, with men affected two to three times as often as women due to alcohol and tobacco use. Alcohol, tobacco use and poor diet taken together are responsible for 90% of head and neck cancer . In addition, human papilloma virus (HPV) was shown to be associated with the development of a unique papillary type of squamous cell carcinoma (SCC) within the upper aerodigestive tract, HPV-16 accounting for 90%-95% of such cases .
In Sudan a recent study showed that oral cancer is the second most occurring cancer among all body cancers . In a previous study of 261 cases of cancer, the most common pattern was
intraoral squamous cell carcinoma (73.6%), with a male to female
ratio of approximately 3:2 .
Squamous cell carcinoma of the head and neck grows locally
and then metastasize to cervical lymph nodes . Cervical
lymph nodes metastasis reduces the survival rate by up to 50%
in patients with SCC of the upper aerodigestive tract [9,10]. The
presence of metastatic cervical lymph nodes is very important in
the prognosis and treatment planning of cancer. Cervical lymph
nodes should be suggested as metastatic in patient with primary
head and neck cancer and treated accordingly. However clinically
palpable lymph nodes might not be metastatic and those were not
detected clinically might be involved histopathological .
Surgical treatment of these oral tumors is excision and
neck dissection . The difficulty in predicting the presence of
metastatic disease in clinically negative necks lead to wide spread
use of elective (prophylactic) neck dissection or radiation ,
increasing the risk of morbidity or even mortality for the patient
Pretreatment evaluation methods, palpation, ultrasonic
tomography (USG) and computed tomography scan (CT scan) for
the neck staging are significantly different from histopathology
results and suggesting that no pretreatment study can accurately
assess the requirement to histopathology .
Computed Tomography (CT) has been available for over a
decade as diagnostic tool to evaluate cervical lymph nodes since
1981 . The Metastatic formula which has been suggested is an
index for cervical lymph nodes assessment in oral and maxillofacial
cancer patients that allows for a more proper treatment .
In this study we aim to assess the validity of this formula
among patients of oral and maxillofacial cancer at Khartoum
Dental Teaching Hospital. Patients will be scored accordingly, and
the score will be correlated with histopathology results.
A prospective descriptive hospital-based study carried out
during the period of 2010 to 2013 at Khartoum Teaching Dental
Hospital, the main referral center of oral and maxillofacial cancer
patients in Sudan. Clinical investigation, CT scan, the Metastasis
Scores (MS); from the CT scan interpretation, was calculated
preoperatively on 25 patients who undergone neck dissection
for primary head and neck malignancy. Exclusion criteria were:
Patient with evidence of distant metastasis (M1), surgically
inoperable patient who will receive palliative care and patient
who are known to be allergic to the CT scan contrast media or
those cannot tolerate the contrast media. Data were collected
from patients, interpretation of CT scan and histopathology
reports. Data were entered in computer using the SPSS software.
All statistical analysis was set at 95%cl, and all test of significance
are two sided.
a. Study plan: CT scan interpretation and assessment: All
CT scans were taken in axial, coronal, and 3D in fine slices and
were evaluated by a single radiologist for the parameters of the
metastasis score (MS), named: Number of the lymph nodes per
region, Shape of the lymph nodes, Presence or absence of central
necrosis, and size of the lymph node.
All the above-mentioned criteria were given a score according
to its metastatic possibility. The total of these scores was called
metastasis score (MS) = lymph nodes number score+ lymph
nodes shape score + lymph nodes necrosis score+ lymph nodes
size score. Patients fulfilling the inclusion and exclusion criteria
were operated in Khartoum Teaching Dental Hospital by a single
expert surgeon. Excised tissues were received and sent for
histopathology lab in 10% formaldehyde as follows; container of
the excised primary lesion for assessment of free surgical margins
and containers labeled according to excised lymph nodes level. All
levels of the lymph nodes were processed and examined by single
expert histopathologist for the presence or absence of malignancy.
Presence of the tumor deposits in any lymph node defines the
entire neck as positive for metastasis.
Ethical issues: Ethical approval was obtained from the Ethical
Committee at Sudan Medical Council and Research Committee
Review Board at the Faculty of Dentistry University of Khartoum
and from the General Directorate of Khartoum Teaching Dental
Hospital. Patients were asked to participate in the study verbally
Results: Twenty-five cases of oral and maxillofacial cancer
patients were investigated for neck metastasis, 12 (48.0%) cases
were positive (+ve) for neck metastasis and 13 (52.0%) cases
were negative (-ve) for neck metastasis in a histopathology result
The frequency for the metastasis score (MS) was taken from
each case individually and from the metastasis score (MS) groups
as classified by the previous study (Table 2 & 3) respectively. No
patients were found to have the metastasis score (MS) 4 and 5.
The histopathology results for the metastasis score group
(0-3) were (-ve) in 7 cases with 100% accuracy as there was no
(+ve) results. For the metastasis score (MS) group (6-10) the
histopathology results were (-ve) in 6 cases with 33.3% accuracy
and it was (+ve) in 12 cases with 66.7% accuracy (Table 4).
The results of this study are statistically significant as P value
= 0.03. The Sensitivity (true +ve results) and specificity (true - ve
results) of this study are 100% and 53% respectively.
The status of the cervical lymph nodes is the single most
important prognostic factor in head and neck cancer . Knowing
whether metastasis is present in the neck is the corner stone in the
treatment of patients. Frequently needless neck dissections are
performed increasing cost and morbidity of patients. According
to Van Den Brakel et al. up to 25% of patients with squamous
cell carcinoma of the head and neck have exclusively micro
metastasis . Evidence of metastases in the neck necessitates
comprehensive clearance of regional lymphatic basins. However,
even if there is no evidence of lymph nodes metastases, when the
risk for positive neck lymph nodes exceeds 15-20% elective neck
dissection is indicated .
CT scan has been used in the staging of head and neck tumors;
evaluating local extension and neck metastasis. The criteria to
consider a neck node positive have been described in several
publications . The present study is aimed to assess the validity
of the metastasis score (MS); a new method for cervical lymph
nodes metastasis, designated in a previous study by Elkulibi &
Suleiman and adopted to assess oral and maxillofacial cancer
patients at Khartoum Teaching Dental Hospital. The present study
is designed to validate and evaluate the accuracy of the metastasis
score (MS) in the assessment of cervical lymph nodes metastasis
in oral and maxillofacial cancer patients.
Twenty-five patients of oral and maxillofacial cancer had
been investigated for cervical lymph nodes metastasis using the
metastasis score (MS) and correlated with histopathology results
for the presence or absence of metastasis. The findings revealed
that 12 (48.0%) cases were positive (+ve) for neck metastasis
and 13 (52.0%) case were negative (-ve) for neck metastasis. Two
patients (8.7%) scored 0, 1(4.0%) patient scored 1, 14 (17.4%)
patients scored 2, 2 (8.7%) patients scored 6, 3 (13.0%) patients
scored 7, 9 (39.1%) patients scored 8 and 4 (16.0%) patients
scored 9. From these findings most of the patients showed high
metastasis score (MS). The authors classified the (MS) into
groups according to its possibility for nodal metastasis, first
group ranging from (0-3), the second group for (MS) = 4, the third
group is for (MS) = 5 and the final group is for (MS) (6-10). In the
present study we have 7 patients (28.0%) in the group (0-3) and
18 (72.0%) patients in the group (6-10).
The resultant scores were correlated with the histopathology
results with a cross tabulation test using the (SPSS) software. The
results showed that the accuracy of the preoperative assessment
of the metastatic status of the cervical lymph nodes in patients
presenting with oral and maxillofacial cancer using the metastatic
score (MS) remains superior to the previous studies and somewhat
compatible with the study to be validated. It showed that the
sensitivity of the assessment for neck metastasis has improved
marginally. This study is consistent with the previous study in the
first group (0-3), showing an accuracy of 100%.
Moreover, for the Metastasis Score (MS) in the group (6-10)
the histopathology results were (-ve) in 6 cases with an accuracy
of 33.3% and was (+ve) in 12 cases with an accuracy of 66.7%.
The histopathology findings in the surgical neck dissections provided convenient results associated with the Metastasis Score
(MS) results. Our findings showed that the Metastasis Score (MS)
can accurately assesses the cervical lymph nodes for metastasis
in the group (0-3) with an accuracy of 100% and for the group
(6-10); with an accuracy of 66.7% and an incidence of 33.3% false
In general, these findings are in close agreement with the
previous study, i.e. the study to be validated, although the sample
doesn’t included Metastasis Score (MS) 4 and 5. Nevertheless, it
suggests that CT scan when performed in the manner described
and interpreted with special attention to the parameters outlined
by the previous study, can provide superior information to
formulate the Metastasis Score (MS).
The increase in false(+ve) incidence rate in the present study
than in the previous study is uncertain although similar methods
were used, such as fine slices of the preoperative CT scan, image
enhancement with an intravenous contrast medium and all the
CT scans were assessed by a single radiologist using the currently
recommended diagnostic criteria. The patients underwent
surgery as soon as possible after the preoperative assessment to
reduce the risk of new tumor growth influencing the results.
Multiple researches had discussed the accuracy of the
diagnostic techniques in assessing the cervical nodes metastasis.
Techniques that in use for the assessment of cervical lymph nodes
metastasis are, clinical palpation, imaging techniques such as CT,
MRI, PET CT scan, SLN biopsy and ultrasound-guided fine needle
aspiration cytology and all of them had been used to improve upon
the results of clinical palpation alone. These diagnostic techniques
showed less than 100% accuracy for neck metastasis and showed
lower sensitivity and Somewhat lower specificity, thus the risk of
occult disease in the neck will remain [10,15-19].
Martinez-Gimeno Scoring System (MGSS) which permits a
risk evaluation for neck metastases in squamous cell carcinoma of
the oral cavity is a histopathology-based scoring system. On their
study in 2010 the authors showed a high sensitivity of 100% and
specificity of 83% in comparison to CT scan and clinical palpation
. Using the Metastasis Score (MS) which is a clinical method
built on a CT scan as a preoperative tool for cervical lymph nodes
assessment is easier than using (MGSS) which is a histopathologybased
scoring system of multiple complicated parameters.
In addition, necrosis of a lymph node (presence of central
hypoattenuation in the lymph nodes on CT scan) is a turning point
in the buildup of the Metastasis Score (MS). It had been strongly
correlated with histopathology results in the previous study as
its presence was the major determinant factor for lymph node
metastasis histopathological, with 100% accuracy .
The presence or absence of necrosis on the CT scan is critical,
as it will add a score of 4 to the formula which will affect the
final Metastasis Score (MS) and increasing the possibility for
metastasis. For example, if the other parameters of the formula
were 0, a positive necrosis will push the final Metastasis Score
(MS) from the first group (0-3), which showed 100% accuracy for
(-ve) metastasis on the histopathology, into group (MS) = 4, which
showed 33% accuracy for (+ve) metastasis.
This novel method of evaluating the cervical lymph nodes
is easy and reliable and allows for a new way to select patients
indicated for neck dissection and sparing those which are
not indicated for neck dissection. In those cases, in which the
probability of metastasis is low we have two options: either a
wait and see policy with a close follow up of the patients; or if
the patient prefers or it is not possible to do a close follow up,
prophylactic neck dissection is indicated. Following this protocol,
we can avoid many needless neck dissections in patients with
head and neck cancer.
a. The present study was based on small sample of patients,
and therefore, the incidence of false (+ve) results for the group (6-
10) may looks big when presented as a percentage and compared
to the previous one.
b. Poor quality CT scans will alter the scoring system as
criterion of necrosis is of paramount importance for the final (MS).
A significant relationship was found between the metastasis
score (MS) and the pathologic status of the neck with 100%
sensitivity and 53% specificity. From the results of the present
study the accuracy of the (MS) for predicting (+ve) histopathology
results in the metastasis score (MS) group (0-3) were 100% and
was 66.7% for the group (6-10) as there were false positive results.
These findings agree with the findings of the previous study.